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Biomedical subjects

J O'Leary

Publications and source records attributed to J O'Leary.

At least 37 records · Page 2Linked to original sources

[Increase of circulating CD3+CD4-CD8-CD19+ cells in the latent phase of HIV-1 infection].

Having reported that HIV-1-infected T cell lines are rescued as CD4- from cytolysis by human complement factor B, we now show the presence of an in vivo counterpart of such CD4- T cells by demonstrating the circulating CD3+ CD4- CD8- CD29+ cells in the blood of seropositive subjects (n = 91, classified by the immunologic scale scores 0, 1, 2 and 3). The cell population was found to be significantly increased in the early phase of infection in score 0: 195/mm3 (p < 0.005) and in score 1:376/mm3 (p = 0.001). With the infection progressing to score 2, the cells decreased to 220/mm3 (p < 0.001) and finally to the same range: 101/mm3, as that of uninfected subjects. Further elucidation of the mechanism of the appearance and disappearance of that population in vivo could help to elucidate protective immunologic processes.

Antigens, CD↗

Pyothorax-associated lymphoma: description of the first two cases detected in Italy.

BACKGROUND: Pyothorax-associated lymphoma (PAL) is a rare, but distinct, clinico-pathologic entity which occurs most often in Japanese people; to the best of our knowledge, only six cases of it have been reported in Western countries. The tumour develops several decades following artificial pneumothorax or chronic pleuritis due to tuberculous infection, produces pleural effusion associated with extensive local lymphomatous infiltrates, and is sustained by a polymorphic large B-cell clonal proliferation showing EBV integration in the genoma of the neoplastic cells. PATIENTS AND METHODS: Herein we describe two cases of PAL observed in Italian patients, both extensively studied on the clinical, pathological, phenotypic, virological, and molecular levels. RESULTS: The two cases occurred, respectively, 45 and 50 years after therapeutic pneumothorax because of tuberculous pleuritis and were characterized by a pleural mass extending to the thoracic wall, which on histological examination were seen to consist of large elements with immunoblastic morphology. Immunohistochemistry show monotypic restriction of Ig light chains, as well as the expression of CD45, B-cell markers (CD20, CD79a, CD45RA), bcl-2 oncogene product, EBNA-2 and, partially, LMP-1. The ratio of cycling cells was extremely high as was the number of mitotic figures. In situ hybridization displayed the presence in the neoplastic cells of the EBV-related small RNAs EBER 1 and 2, which in turn, along with the positivity for EBNA-2 and LMP-1, further strengthened the close relationships between PAL and latent viral infection. Molecular studies revealed, on one hand, clonal rearrangement of the Ig heavy chain J region genes, and on the other, negativity for HHV8 in one case and positivity in the other. CONCLUSIONS: These cases of PAL are the first to be documented in Italy; they serve to direct attention to the fact that this condition is not confined to Japanese people, and that its occurrence in Western countries might be underestimated.

Aged↗

Surrogate marker of preclinical tuberculosis in human immunodeficiency virus infection: antibodies to an 88-kDa secreted antigen of Mycobacterium tuberculosis.

Antibodies to purified, size-fractionated secreted proteins of Mycobacterium tuberculosis in sera from patients with human immunodeficiency virus (HIV) infection and active tuberculosis (HIV/TB patients), and in stored sera obtained from the same patients prior to clinical manifestation of TB, were evaluated by ELISA, and the repertoire of antigens recognized was analyzed by immunoblotting. Compared with non-HIV/TB patients, HIV/TB patients had lower levels of anti-mycobacterial antibodies, and these were directed toward a restricted set of antigens. Antibodies to an 88-kDa secreted antigen were present in the sera of 74% of HIV/TB patients during the years (1.5-6) prior to manifestation of active, clinical tuberculosis, although only 66% were positive by the time tuberculosis was diagnosed. The presence of antibodies to the 88-kDa antigen can serve as a surrogate marker for identifying HIV-infected persons with active, subclinical disease who are at a high risk of developing clinical tuberculosis.

Antibodies, Bacterial↗

Health insurance plans from the consumer's point of view: the good one and the bad one.

This article describes two personal experiences with health maintenance organizations (HMO) that occurred over the past two years. The first is a positive experience and the second a negative experience. In the first encounter, the HMO worked with the client. In the second encounter, the insurance did not work with its client. This article shows that partnerships developed at administrative levels within these organizations can affect the multiple barriers and obstacles that currently exist in many HMOs.

Cost Control↗

Serotyping of primary human immunodeficiency virus type 1 isolates from diverse geographic locations by flow cytometry.

The immunologic relatedness of the various human immunodeficiency virus type 1 (HIV-1) clades was determined with 13 human anti-HIV-1 monoclonal antibodies (MAbs) to six immunogenic regions of the HIV-1 structural proteins. The immunoreactivity of the native, oligomeric viral envelope glycoproteins expressed on the surfaces of human peripheral blood mononuclear cells infected in vitro with primary isolates from clades A through E was determined by flow cytometry. Some epitopes in the immunodominant region of gp41 and the C terminus of gp120 appear to be HIV-1 group specific in that they are expressed on the surfaces of cells in cultures infected with the majority of viruses tested from clades A to E. Epitopes within the V3 region appear to be clade restricted. Surprisingly, one MAb to an epitope in the C terminus of gp120 was entirely clade B specific. Staining with anti-V2 and anti-CD4 binding domain (CD4bd) reagents was infrequently detected. Anti-CD4bd MAbs stained only CD4-negative T cells because the CD4bd of gp120 appeared to be complexed with membrane CD4. When present, the epitopes of V2 and the CD4bd appeared to be expressed on cells infected with various clades. Thus, the results suggest that MAbs to gp41, the C terminus, and the V3 loop of gp120 are most useful in serotyping primary isolates of HIV-1, providing group-specific, clade-restricted, and clade-specific reagents. The use of the immunofluorescent method with the reagents described herein distinguishes infection with clade B from that with all other HIV-1 clades. With additional MAbs, this technique will allow a broadly applicable, reproducible, and practical method for serotyping HIV-1.

Amino Acid Sequence↗

Cardiovascular and respiratory effects of endothelin in the ventrolateral medulla of the normotensive rat.

We studied the relevance of the ventrolateral medulla for the cardiovascular and respiratory effects of endothelin-1 in urethane-anesthetized rats. Microinjection of endothelin-1 into the rostral ventrolateral medulla (RVLM) evoked pressor and bradycardic effects followed by sustained decreases in blood pressure, bradycardia, and respiratory depression. These effects were inhibited by endothelin-A receptor antagonists (BQ-123 and BQ-610) but not by endothelin-B antagonists. In the caudal ventrolateral medulla (CVLM) endothelin-1 decreased blood pressure, renal sympathetic nerve activity, respiratory frequency, and phrenic nerve activity, whereas heart rate increased. Pretreatment with BQ-123 in the CVLM increased respiratory frequency by 15 +/- 6 breaths per minute and prevented the effects of intra-CVLM administration of endothelin-1. In separate experiments, the intracisternal administration of endothelin-1 (20 pmol) to rats pretreated with saline in both RVLM and CVLM resulted in a hypotensive and bradycardic phase that was followed by hypertension (50 +/- 15 mm Hg), bradycardia, and 100% mortality. In a separate group, pretreatment with BQ-123 in the RVLM and CVLM completely inhibited the hypotensive phase and reduced by 83% the subsequent rise in blood pressure evoked by endothelin-1. Cardiorespiratory arrest was prevented in all the rats in this group. Selective endothelin receptor blockade in the RVLM attenuated the hypertensive period of intracisternal administration of endothelin-1 and prevented mortality by 33%, whereas in the CVLM the endothelin receptor antagonist inhibited the initial hypotension and reduced mortality by 25%. Our results support the concept that in the ventral medulla, endothelin-1 can modulate cardiovascular and respiratory function.

Animals↗

Use of whole bowel irrigation in an infant following iron overdose.

An 11-month-old, 11-kg infant presented to the emergency department after ingesting 130 to 150 mg/kg of elemental iron. Emesis was induced twice and the child was lavaged throughout a 4-hour period with some tablet return. An abdominal radiograph after gastrointestinal decontamination showed at least 16 whole iron tablets remaining in the stomach. Serum iron drawn 2 hours postingestion was 46.7 mumol/L. Blood glucose was 7.7 mmol/L and white blood count was 21,800 mm3. Despite a second lavage 8 hours postingestion, a large number of whole tablets were visualized in the stomach per radiograph. Whole bowel irrigation with polyethylene glycol electrolyte lavage solution (Golytely, Braintree Laboratories, Inc, Braintree, MA) was begun via nasogastric tube 14 hours after the ingestion. Serial abdominal radiographs showed tablet movement out of the stomach within 4 hours after initiating whole bowel irrigation. This case demonstrates the safety and efficacy of WBI in an infant when conventional gastrointestinal decontamination has failed.

Deferoxamine↗

Human nidogen gene: structural and functional characterization of the 5'-flanking region.

Nidogen is a sulfated multifunctional glycoprotein present in basement membranes. In this study, we have cloned the 5'-flanking region of the human nidogen gene. Initially, an approximately 35-kb DNA clone (NCos4) was isolated from a human cosmid genomic library. Southern hybridization of EcoRI-digested NCos4 allowed isolation of a 3.7-kb fragment, which was shown to contain a portion of intron 1, the entire exon 1, and approximately 0.9 kb of 5'-flanking sequences of the nidogen gene. Nucleotide sequencing of the 5'-flanking DNA revealed the presence of two canonic CCAAT consensus sequences in the antisense strand and a potential variant of the TATA motif, TATTT, in the sense strand. One putative AP-2 and six putative SP1 binding sites were also present. To test the functional promoter activity of the 5'-flanking genomic DNA, two nidogen promoter/CAT reporter gene constructs, with the promoter segment spanning from -864 to -1 and from -534 to -1, respectively, were developed and analyzed in transient transfections of human and mouse cell cultures. Both constructs showed clearly detectable promoter activity, and the activity of the larger construct could be up-regulated by 12-O-tetradecanoyl phorbol 13-acetate up to 2.5 times. The results indicate that the nidogen promoter/CAT gene constructs developed in this study provide a means to examine the transcriptional regulation of nidogen gene expression in human diseases of the basement membrane zone.

Amino Acid Sequence↗

Hurler's disease with diastematomyelia.

A case of Hurler's disease is reported in a child with a gibbous deformity of the lumbar vertebrae L1/L2 and a localized diastematomyelia of the spinal cord at L1/L3. The association of an enzyme disorder affecting connective tissue with spinal cord dysraphism has not been reported before, and may be fortuitous. However, as each condition is rare, the occurrence of both gibbous deformity due to Hurler's and diastematomyelia in the same child, makes it unlikely to be a chance association. We suggest that defective neurulation in this case may be related to mesodermal damage associated with mucopolysaccharidosis.

Brain↗

The vital link-up.

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Administrative Personnel↗

Calcium antagonists in the treatment of Tourette's disorder.

Two patients with Tourette's disorder were treated with calcium antagonists. Verapamil and nifedipine produced positive responses, and diltiazem produced no response. Given the negative side effects of the current drugs for this disorder, the authors suggest further study of calcium antagonists.

Adult↗